1. Fundamentals of Tuberculosis (TB)
Appendix 12 - Fundamentals of TB Presentation
Fundamentals of Tuberculosis (TB)

2. Appendix 12 - Fundamentals of TB Presentation
TB in the United States
From 1953 to 1984, reported cases decreased by approximately 5.6% each year
From 1985 to 1992, reported cases increased by 20%
25,313 cases reported in 1993
Since 1993, cases are steadily declining

3. Factors Contributing to the Increase in TB Cases
Appendix 12 - Fundamentals of TB Presentation
Factors Contributing to the Increase in TB Cases
HIV epidemic
Increased immigration from high-prevalence countries
Transmission of TB in congregate settings (e.g., correctional facilities, long term care)
Deterioration of the public health care infrastructure

4. Transmission and Pathogenesis of TB
Appendix 12 - Fundamentals of TB Presentation
Transmission and Pathogenesis of TB
Caused by Mycobacterium tuberculosis (M. tuberculosis)
Spread person to person through airborne particles that contain M. tuberculosis, called droplet nuclei
Transmission occurs when an infectious person coughs, sneezes, laughs, or sings
Prolonged contact needed for transmission
10% of infected persons will develop TB disease at some point in their lives

5. Appendix 12 - Fundamentals of TB Presentation
Sites of TB Disease
Pulmonary TB occurs in the lungs
85% of all TB cases are pulmonary
Extrapulmonary TB occurs in places other than the lungs, including the:
Larynx
Lymph nodes
Brain and spine
Kidneys
Bones and joints
Miliary TB occurs when tubercle bacilli enter the bloodstream and are carried to all parts of the body

6. Appendix 12 - Fundamentals of TB Presentation
Not Everyone Exposed
Becomes Infected
Probability of transmission depends
on:
Infectiousness
Type of environment
Length of exposure
10% of infected persons will develop
TB disease at some point in their lives
5% within 1-2 years
5% at some point in their lives

7. Persons at Risk for Developing TB Disease
Appendix 12 - Fundamentals of TB Presentation
Persons at Risk for Developing TB Disease
Persons at high risk for developing TB disease fall into 2 categories
Those who have been recently infected
Those with clinical conditions that increase their risk of progressing from LTBI to TB disease

8. Recent Infection as a Risk Factor
Appendix 12 - Fundamentals of TB Presentation
Recent Infection as a Risk Factor
Persons more likely to have been recently infected include
Close contacts to persons with infectious TB
Skin test converters (within past 2 years)
Recent immigrants from TB-endemic areas (within 5 years of arrival to the U.S.)
Children ≤ 5 years with a positive TST
Residents and employees of high-risk congregate settings (e.g. correctional facilities, homeless shelters, healthcare facilities)

9. Increased Risk for Progression to TB Disease
Appendix 12 - Fundamentals of TB Presentation
Increased Risk for Progression to TB Disease
Persons more likely to progress from LTBI to TB disease include
HIV infected persons
Those with history of prior, untreated TB
Underweight or malnourished persons
Injection drug use
Those receiving TNF-α antagonists for treatment of rheumatoid arthritis or Crohn’s disease
Certain medical conditions

10. Appendix 12 - Fundamentals of TB Presentation
Latent TB Infection (LTBI)
Occurs when person breathes in bacteria
and it reaches the air sacs (alveoli) of lung
Immune system keeps bacilli contained
and under control
Person is not infectious and has no
symptoms

11. Appendix 12 - Fundamentals of TB Presentation
TB Disease
Occurs when immune system cannot
keep bacilli contained
Bacilli begin to multiply rapidly
Person develops TB symptoms

12. Appendix 12 - Fundamentals of TB Presentation
LTBI vs. TB Disease
LTBI
TB Disease
Tubercle bacilli in the body
TST or QFT-Gold® result usually positive
Chest x-ray usually normal
Chest x-ray usually abnormal
Sputum smears and cultures negative
Symptoms smears and cultures positive
No symptoms
Symptoms such as cough, fever, weight, loss
Not infectious
Often infectious before treatment
Not a case of TB
A case of TB

13. Appendix 12 - Fundamentals of TB Presentation
Targeted Testing
Detects persons with LTBI who would benefit from treatment
De-emphasize testing of groups of people who are not at risk (mass screening)
Consider using a risk assessment tool
Testing should be done only if there is an intent to treat
Can help reduce the waste of resources and prevent unnecessary treatment

14. Groups to Target with the Tuberculin Skin Test
Appendix 12 - Fundamentals of TB Presentation
Groups to Target with the Tuberculin Skin Test
Persons with or at risk for HIV infection
Close contacts of persons with infectious TB
Persons with certain medical conditions
Injection drug users
Foreign-born persons from areas where TB is common
Medically underserved, low-income populations
Residents of high-risk congregate settings
Locally identified high-prevalence groups

15. Appendix 12 - Fundamentals of TB Presentation
Administering the TST
Use Mantoux tuberculin skin test
0.1 mL of 5-TU of purified protein derivative (PPD) solution injected intradermally
Use a 27 gauge needle
Produce a wheal that is 6-10mm in diameter

16. Appendix 12 - Fundamentals of TB Presentation
Reading the TST
Read within hours
Measure induration, not erythema
Positive reactions can be measured accurately for up to 7 days
Negative reactions can be read accurately for only 72 hours

17. Appendix 12 - Fundamentals of TB Presentation
TST Interpretation - 1
5 mm of induration is positive in:
HIV-infected persons
Close contacts to an infectious TB case
Persons who have chest x-ray findings consistent with prior untreated TB
Organ transplant recipients
Persons who are immunosuppressed (e.g., those taking the equivalent of >15 mg/d of prednisone for 1 month or those taking TNF-α antagonists)

18. Appendix 12 - Fundamentals of TB Presentation
TST Interpretation - 2
10 mm induration is positive in:
Recent immigrants (within last 5 years) from a high-prevalence country
Injection drug users
Persons with other high-risk medical conditions
Residents or employees of high-risk congregate settings
Mycobacteriology laboratory personnel
Children < 4 years of age; infants, children, and adolescents exposed to adults at high risk

19. Appendix 12 - Fundamentals of TB Presentation
TST Interpretation - 3
15 mm induration is positive in:
Persons with no known risk factors for TB

20. Appendix 12 - Fundamentals of TB Presentation
Recording TST Results
Record results in millimeters of induration, not “negative” or “positive”
Only trained healthcare professionals should read and interpret TST results

21. False Positive TST Reactions
Appendix 12 - Fundamentals of TB Presentation
False Positive TST Reactions
Nontuberculous mycobacteria
Reactions are usually ≤10mm of induration
BCG vaccination
Reactivity in BCG vaccine recipients generally wanes over time
Positive TST results is likely due to TB infection if risk factors are present
BCG-vaccinated persons with positive TST result should be evaluated for treatment of LTBI
QFT is able to distinguish M.tb from other mycobacteria and BCG vaccine

22. False Negative TST Reactions
Appendix 12 - Fundamentals of TB Presentation
False Negative TST Reactions
Anergy, or inability to react to TST because of weakened immune system
Recent TB infection (2-10 weeks after exposure)
Very young age (newborns)
Recent live-virus vaccination can temporarily suppress TST reactivity
Poor TST administration technique (too shallow or too deep, or wheal is too small)

23. Appendix 12 - Fundamentals of TB Presentation
Boosting
Some people with history of LTBI lose their ability to react to tuberculin (immune system “forgets” how to react to TB-like substance, i.e., PPD)
Initial TST may stimulate (boost) the ability to react to tuberculin
Positive reactions to subsequent tests may be misinterpreted as new infections rather than “boosted” reactions

24. Appendix 12 - Fundamentals of TB Presentation
Two-Step Testing - 1
A strategy for differentiating between boosted reactions and reactions caused by recent TB infection
Use two-step testing for initial (baseline) skin testing of adults who will be re-tested periodically
2nd skin test given 1-3 weeks after baseline

25. Appendix 12 - Fundamentals of TB Presentation
Two-Step Testing - 2
If the 1st TST is positive, consider the person infected
If the 1st TST is negative, administer 2nd TST in 1-3 weeks
If the 2nd TST is positive, consider the person infected
If the 2nd TST is negative, consider the person uninfected at baseline

26. Appendix 12 - Fundamentals of TB Presentation
Infectiousness - 1
Patients should be considered infectious if they:
Are undergoing cough-inducing procedures
Have sputum smears positive for acid-fast bacilli (AFB) and:
Are not receiving treatment
Have just started treatment, or
Have a poor clinical or bacterial response to treatment
Have cavitary disease
Extrapulmonary TB patients are not infectious

27. Appendix 12 - Fundamentals of TB Presentation
Infectiousness - 2
Patients are not considered infectious if they meet all these criteria:
Received adequate treatment for 2-3 weeks
Favorable clinical response to treatment
3 consecutive negative sputum smears results from sputum collected on different days

28. Techniques to Decrease TB Transmission
Appendix 12 - Fundamentals of TB Presentation
Techniques to Decrease TB Transmission
Instruct patient to:
Cover mouth when coughing or sneezing
Wear mask as instructed
Open windows to assure proper ventilation
Do not go to work or school until instructed by physician
Avoid public places
Limit visitors
Maintain home or hospital isolation as ordered

29. Appendix 12 - Fundamentals of TB Presentation
Evaluation for TB
Medical history
Physical examination
Mantoux tuberculin skin test
Chest x-ray
Bacteriologic exam (smear and culture)

30. Appendix 12 - Fundamentals of TB Presentation
Symptoms of TB
Productive prolonged cough*
Chest pain*
Hemoptysis*
Fever and chills
Night sweats
Fatigue
Loss of appetite
Weight loss
*Commonly seen in cases of pulmonary TB

31. Appendix 12 - Fundamentals of TB Presentation
Chest x-Ray
Obtain chest x-ray for patients with positive TST results or with symptoms suggestive of TB
Abnormal chest x-ray, by itself, cannot confirm the diagnosis of TB but can be used in conjunction with other diagnostic indicators

32. Appendix 12 - Fundamentals of TB Presentation
Sputum Collection
Sputum specimens are essential to confirm TB
Specimens should be from lung secretions, not saliva
Collect 3 specimens on 3 different days
Spontaneous morning sputum more desirable than induced specimens
Collect sputum before treatment is initiated

33. Appendix 12 - Fundamentals of TB Presentation
Smear Examination
Strongly consider TB in patients with smears containing acid-fast bacilli (AFB)
Use subsequent smear examinations to assess patient’s infectiousness and response to treatment

34. Appendix 12 - Fundamentals of TB Presentation
Culture
Used to confirm diagnosis of TB
Culture all specimens, even if smear is negative
Initial drug isolate should be used to determine drug susceptibility

35. Treatment of Latent TB Infection
Appendix 12 - Fundamentals of TB Presentation
Treatment of Latent TB Infection
Daily Isoniazid therapy for 9 months
Monitor patients for signs and symptoms of hepatitis and peripheral neuropathy
Alternate regimen – Rifampin for 4 months

36. Treatment of TB Disease
Appendix 12 - Fundamentals of TB Presentation
Treatment of TB Disease
Include four 1st-line drugs in initial regimen
Isoniazid (INH)
Rifampin (RIF)
Pyrazinamide (PZA)
Ethambutol (EMB)
Adjust regimen when drug susceptibility results become available or if patient has difficulty with any of the medications
Never add a single drug to a failing regimen
Promote adherence and ensure treatment completion

37. Directly Observed Therapy (DOT)
Appendix 12 - Fundamentals of TB Presentation
Directly Observed Therapy (DOT)
Health care worker watches patient swallow each dose of medication
DOT is the best way to ensure adherence
Should be used with all intermittent regimens
Reduces relapse of TB disease and acquired drug resistance

38. Appendix 12 - Fundamentals of TB Presentation
Clinical Monitoring
Instruct patients taking TB medications to immediately report the following:
Rash
Nausea, loss of appetite, vomiting, abdominal pain
Persistently dark urine
Fatigue or weakness
Persistent numbness in hands or feet

39. Appendix 12 - Fundamentals of TB Presentation
Drug Resistance
Primary - infection with a strain of M. tuberculosis that is already resistant to one or more drugs
Acquired - infection with a strain of M. tuberculosis that becomes drug resistant due to inappropriate or inadequate treatment

40. Appendix 12 - Fundamentals of TB Presentation
Barriers to Adherence
Stigma
Extensive duration of treatment
Adverse reactions to medications
Concerns of toxicity
Lack of knowledge about TB and its treatment

41. Appendix 12 - Fundamentals of TB Presentation
Improving Adherence
Adherence is the responsibility of the provider, not the patient and can be ensured by:
Patient education
Directly observed therapy (DOT)
Case management
Incentives/enablers

42. Measures to Promote Adherence
Appendix 12 - Fundamentals of TB Presentation
Measures to Promote Adherence
Develop an individualized treatment plan for each patient
Provide culturally and linguistically appropriate care to patient
Educate patient about TB, medication dosage, and possible adverse reactions
Use incentives and enablers to address barriers
Facilitate access to health and social services

43. Appendix 12 - Fundamentals of TB Presentation
Completion of Therapy
Based on total number of doses administered, not duration of treatment
Extend or re-start if there were frequent or prolonged interruptions

44. Appendix 12 - Fundamentals of TB Presentation
Meeting the Challenge
Prevent TB by assessing risk factors
If risk is present, perform TST
If TST is positive, rule out active disease
If active disease is ruled out, initiate treatment for LTBI
If treatment is initiated, ensure completion

45. Appendix 12 - Fundamentals of TB Presentation
Remember
“A decision to test is a decision to treat.”